The Philadelphia negative myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia, and myelofibrosis, are associated with substantial vascular and transformative complications. Standard therapy for high-risk disease, particularly in patients that have failed initial therapy, remains controversial. Non-pegylated interferon has previously been shown to be effective in controlling erythrocytosis, thrombocytosis and thrombotic complications, but was found to have poor tolerability and excessive adverse effects. Recently, pegylated interferon alpha-2a was introduced and found to be better tolerated and less toxic than standard interferon. In addition, in recent phase II trials, pegylated interferon alpha-2a therapy was found to induce both hematologic and molecular remissions. We retrospectively analyzed 118 myeloproliferative patients who underwent pegylated interferon alpha-2a treatment. Responses were evaluated by ELN, IWG-MET and EUMNET standardized criteria sets and adverse effects were analyzed.